You are here

  • Home
  • Archive
  • Volume 9, Issue 11
  • Vitamin C therapy for patients with sepsis or septic shock: a protocol for a systematic review and a network meta-analysis

Article Text

Article menu

Download PDFPDF

XML
Intensive care
Protocol
Vitamin C therapy for patients with sepsis or septic shock: a protocol for a systematic review and a network meta-analysis
  1. Tomoko Fujii1,2,
  2. Alessandro Belletti3,4,
  3. Anitra Carr5,
  4. Toshi A Furukawa2,
  5. Nora Luethi1,6,
  6. Alessandro Putzu7,
  7. Chiara Sartini3,
  8. Georgia Salanti8,
  9. Yasushi Tsujimoto9,10,
  10. Andrew A Udy1,11,
  11. Paul J Young12,13,
  12. Rinaldo Bellomo1,4,14
  1. 1Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
  2. 2Department of Health Promotion and Human Behaviour, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, Japan
  3. 3Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
  4. 4Department of Intensive Care, Austin Hospital, Heidelberg, Victoria, Australia
  5. 5Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand
  6. 6Oncology, Inselspital University Hospital Bern, Bern, Switzerland
  7. 7Division of Anesthesiology, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland
  8. 8Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
  9. 9Department of Healthcare Epidemiology, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, Japan
  10. 10Department of Nephrology and Dialysis, Kyoritsu Hospital, Kawanishi, Japan
  11. 11Department of Intensive Care, the Alfred, Melbourne, Victoria, Australia
  12. 12Medical Research Institute of New Zealand, Wellington, New Zealand
  13. 13Intensive Care Unit, Wellington Regional Hospital, Wellington, New Zealand
  14. 14Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
  1. Correspondence to Dr Tomoko Fujii; tomoko.fujii{at}monash.edu

Abstract

Introduction Vasoplegia is common and associated with a poor prognosis in patients with sepsis and septic shock. Vitamin C therapy in combination with vitamin B1 and glucocorticoid, as well as monotherapy in various doses, has been investigated as a treatment for the vasoplegic state in sepsis, through targeting the inflammatory cascade. However, the combination effect and the relative contribution of each drug have not been well evaluated. Furthermore, the best combination between the three agents is currently unknown. We are planning a systematic review (SR) with network meta-analysis (NMA) to compare the different treatments and identify the combination with the most favourable effect on survival.

Methods and analysis We will include all randomised controlled trials comparing any intervention using intravenous vitamin C, vitamin B1 and/or glucocorticoid with another or with placebo in the treatment of sepsis. We are interested in comparing the following active interventions. Very high-dose vitamin C (≥12 g/day), high-dose vitamin C (≥6 g/day), vitamin C (<6 g/day); low-dose glucocorticoid (<400 mg/day of hydrocortisone (or equivalent)), vitamin B1 and combinations of the drugs above. The primary outcome will be all-cause mortality at the longest follow-up within 1 year but 90 days or longer postrandomisation. All relevant studies will be sought through database searches and trial registries. All reference selection and data extraction will be conducted by two independent reviewers. We will conduct a random-effects NMA to synthesise all evidence for each outcome and obtain a comprehensive ranking of all treatments. We will use the surface under the cumulative ranking curve and the mean ranks to rank the various interventions. To differentiate between the effect of combination therapies and the effect of a component, we will employ a component NMA.

Ethics and dissemination This SR does not require ethical approval. We will publish findings from this systematic review in a peer-reviewed scientific journal and present these at scientific conferences.

PROSPERO registration number CRD42018103860.

  • adult intensive & critical care
  • clinical trials
  • statistics & research methods

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2019-033458

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Twitter @Toshi_FRKW

    • Contributors TF, AC, NL, PJY and RB devised the study. TF drafted the protocol, will assist with the data collection and will draft the results and discussion. AC, TAF, GS, AAU, PJY and RB revised the protocol, assisted with study design and will help draft the final manuscript. AB, NL, AP, CS and YT revised the protocol and will carry out the data collection. TF will carry out the statistical analysis with the inputs from GS and will be the guarantor of the review. All authors gave final approval of the version to be published and agreed to be accountable for all aspects of this work.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests TF, NL, AAU, PJY and RB are part of the management committee of VITAMINS trial (NCT 03333278). AC is supported by a Health Research Council of New Zealand Sir Charles Hercus Health Research Fellowship. TAF reports personal fees from Mitsubishi-Tanabe and MSD, and a grant from Mitsubishi-Tanabe, outside the submitted work; TAF has a patent 2018-177688 pending. GS was invited and participated on two methods for real world evidence meetings organised by Merck and Biogen.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.